Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• , because of their particular chemical and physical properties [15]. In addition to ester/amide synthesis, enoyl imidazolides were developed as excellent Michael acceptors. Acylimidazoles are unique electrophiles that demonstrate moderate reactivity, relatively high stability, chemical selectivity, and high

• ]. These non-traditional electrophiles allow access to structurally highly interesting motifs. In addition, they are amenable to valuable synthetic transformations such as oxidative ring contraction of the cycloheptatrienyl ring or reduction of the benzodithiolyl group. In this context, we decided to study

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• with 1° alkyl electrophiles has been known in the past, however, the C–H alkylation with nonactivated secondary (2°) alkyl electrophiles and tertiary alkyl electrophiles was little known. In this context, in 2013, Fu and co-workers came across an unexpected finding with Pd-catalyzed C–H activation/C–C

• cross-coupling of pyridine N-oxides with nonactivated secondary (2°) alkyl bromides [51]. The cross-coupling is difficult to achieve as the Pd-catalyzed SN2 process is sensitive towards the steric bulk of the secondary or tertiary alkyl electrophiles. The optimized conditions for the ortho-alkylation of

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• years of development. The effort of our group to broaden possibilities to engage metal enolates in reactions with new electrophiles is described. The material is divided according to the organometallic reagent employed in the conjugate addition step, and thus to the particular metal enolate formed

• stereogenic information, thus leading to chiral products. Enolate species are uniquely positioned for reactivity with a broad array of electrophiles and thus allowing quick and efficient construction of highly complex structures from readily available starting materials. Various polar organometallic reagents

• nucleophile (R3Zn−) to the ketone with moderate yields but still good stereoselectivities (Scheme 9B). In 2018, Wang and co-workers extended the group of applicable electrophiles for the zinc enolate-based tandem reactions. Following the conjugate addition of Et2Zn to acyclic α,β-unsaturated ketones 41, they

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• thermodynamically controlled stereoselectivity as compared to the parent Belokon complex. Additionally, functionalization with the tert-butyl group significantly enhances the reactivity of the deprotonated glycine complex towards electrophiles as compared to the anionic species formed from the original Belokon

• chemical transformations. The oxidation potential value of the deprotonated glycine complex correlates with the reactivity of the α-carbanionic species towards electrophiles [37]. Therefore, the electrochemical approach is very convenient and informative for the estimation of the relative reactivity of the

• determined previously for the parent Belokon complex (GlyNi)L1 (−0.32 V vs Ag/AgCl/KCl(sat.) [37]) and (GlyNi)L4 (−0.22 V [37]) showed that the nucleophilic equivalent of (GlyNi)L7 (Eox = −0.41 V, see Table 4) should be much more reactive towards electrophiles than the deprotonated (GlyNi)L1 and (GlyNi)L4

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• intercepted by an electrophile to generate the difunctionalized system. This methodology has been applied several times to strained bicyclic alkenes with a variety of electrophiles. In 2015, Hirano and Miura developed a Cu-catalyzed aminoboration of bicyclic alkenes 1 with bis(pinacolato)diboron (B2pin2) (53

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• transborylation with HBpin, to give the thioBpin 77 product and regenerate the amine-borane catalyst 73 (Scheme 17). Yamamoto reported the borane-catalysed hydroalumination of alkenes and allenes (Scheme 18) [80][81][82][83] in which the organoaluminium products were reacted in situ with various electrophiles to

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• polymerization (CROP) of the respective 2-substituted 2-oxazoline (Figure 1) initiated with various electrophiles [18][19][20][21]; most commonly alkyl tosylates or triflates are applied [21][22][23][24]. The use of suitable solvents plays a significant role in obtaining well-defined polymers with a narrow molar

• NMR spectra (Figure S6), indicating no interaction between the solvent and the monomer. Polymerization of 2-ethyl-2-oxazoline Six different electrophiles, acetyl chloride (AcCl), propionyl chloride (PrCl), benzyl bromide (BnBr), MeOTf, MeOTs, and EtOxMeOTf, were examined as initiators for the EtOx

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• could afford satisfying coupling yields by a suitable variation of the nature of the leaving group. In 2008, Cahiez reported an iron-catalyzed alkenylation of organomagnesium reagents with enol phosphates as electrophiles, instead of alkenyl halides [19]. In this case, when reactive enol phosphates

• ) as a co-solvent. Nevertheless, capitalizing on these results, Cahiez further developed this iron-catalyzed cross coupling reaction with dienol phosphates as electrophiles, which are thermally more stable than dienyl halides [20]. It was found that when dienol phosphates were used as electrophiles

• 1 by the M2i Company. Magnesium alkoxides used as additives Although it can lead to efficient NMP-free cross-coupling procedures, the use of enol phosphates as coupling electrophiles also brings several issues for efficient and sustainable procedures meant to be carried out at large scales. First

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• highly reactive electrophiles. The homologous 1,4-dithianes or 1,4-dioxanes are readily available as simple building blocks, but also undergo a swift β-elimination following the metalation of one of their ring carbons, again limiting their appeal as building blocks [16][17]. In his landmark synthesis of

• expected fragmentation (Scheme 6e) [42]. The metalated dihydrodithiins can thus also be reacted with less activated electrophiles, including secondary alkylating agents. As we shall discuss in chapter 4, this makes 5,6-dihydro-1,4-dithiins the most suitable building blocks for Corey–Seebach-type

• opens up options for Corey–Seebach-type alkylation reactivity with a wider range of electrophiles. The method is demonstrated by the smooth lithiation and subsequent alkylation of the acetophenone-derived dithiin 50 (Scheme 10a) [42]. Palumbo’s elegant overall approach to dihydrodithiin-mediated

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• enolate was treated with 4-nitrobenzaldehyde to promote the aldolization reaction but the corresponding alcohol was not observed, which confirmed the reluctance of 6a·Li to react with other electrophiles than protons. Unable to form the quaternary carbon of the target from this intermediate, the pathway

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• a nucleophilic reacting center. In addition to umpolung reactions with electrophiles, Breslow intermediates can undergo oxidation with the formation of radical cations or electrophilic acylazolium cations. The acylazolium cation in turn can undergo nucleophilic attack resulting in C–O and C–N

• , organocatalysis by the modulation of redox properties of reagents has much in common with redox-neutral organocatalysis. With the exception of free-radical processes, the distinguishing feature of these organocatalyzed oxidations frequently lies in the involvement of peroxides as O-nucleophiles or O-electrophiles

• instead of corresponding C-nucleophiles or C-electrophiles in redox-neutral organocatalyzed reactions. Organocatalysis by redox-active organic molecules N-Oxyl radical catalysis Reactive N-oxyl radicals generated in situ from the corresponding N-hydroxy compounds have found numerous applications in CH

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• more nucleophilic than the N9 atom. It comes out that the N7-nitrogen in the adenine anion reacts more readily with electrophiles, i.e., nucleophilic reactions occur preferably at the N7-position. The same conclusion was made by Stachowicz–Kuśnierz and Korchowiec who have shown that the inherent

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• ). With the 3-silylated 2-furyl carbinol substrates at hand, we then considered C–Si bond activation strategies relying on the assistance of the oxygen atom to promote electrophilic substitution reactions with carbon electrophiles. C3–Si bond functionalization through intramolecular activation by

• of electrophiles to deliver product D, resulting from the overall C2–Si functionalization (Scheme 3, top) [24][25]. The key to the viability of this process is the formation of pentavalent silicon intermediate B. This suggested that a related pentavalent intermediate F could be similarly accessible

• furan rings, which gave products 25 and 26 in 42% and 40% yield, respectively. Electrophiles other than methallyl chloride could also be used. C3-Allylation of substrate 4c, leading to 27, was achieved in 52% yield by reaction with allyl chloride and in a better 61% yield using allyl bromide. It should

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• ), global softness (S), electronic chemical potential (µ), electrophilicity (ω) and nucleophilicity (N) indices of 2-phosphaindolizines 6 and 1,3-butadiene (7) are given in Table 2. 2-Phosphaindolizines and 1,3-butadiene are soft electrophiles and nucleophile, respectively, and in accordance with the HSAB

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• reactions with electrophiles, intramolecular cyclization and disproportionation process. The synthetic viability of the approach will be considered. A one-pot multistep synthetic protocol is suggested, based on addition of thiols to the mixture of isomeric alkenes formed in an electroreductive opening of a

• well as to steric reasons. Reaction with electrophiles Anions formed in the reductive ring opening in complex 4 are stable enough: they survive even in the presence of acetic acid and do not react with electrophiles (CH3I, benzaldehyde). In contrast, addition of external electrophiles in the reaction

• that follow-up functionalization of the anions formed after the ring opening with electrophiles (except H+) has low synthetic value due to multiple competing reaction channels observed in case of 3 and decreased nucleophilicity of 4. Consequently, it seems reasonable to focus on the one-pot

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• catalytic amount of transition-metal reductants have been developed, but stoichiometric silicon electrophiles and co-reductants such as Zn were commonly required to complete the catalytic cycle [14]. More recently, visible light-mediated pinacol coupling reactions have been disclosed by several groups [15

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• ], the strategy is the dearomatizing anionic cyclization of diaryl-N-alkyl-N-benzylphosphinamides by treatment with sec-butyllithium followed by reactions with different electrophiles, such as water, alcohols, alkyl halides, aldehydes, etc. They first realized the dearomatizing anionic cyclization of

• hindrance of the N-alkyl group, although several regio- and diastereoisomers were generated in the reactions (Scheme 22) [19]. They further investigated the influences of the time of metalation, the concentration of base, cosolvents (additives), and the time of contact with the electrophiles on the regio

• - and stereoselectivities in the tandem intramolecular nucleophilic dearomatization of diphenyl-N-alkyl-N-benzylphosphinamides and reactions with different electrophiles under various reaction conditions [47]. They used both racemic and enantiopure diphenyl-N-methyl-N-(1-phenylethyl)phosphinamides 124

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• diastereomeric products 3 were obtained. Compared with previously reported methods, our current method is more convenient and low cost without any activators (such as thionyl chloride, sulfonyl chlorides, NBS, electrophiles, and radical initiators) and catalysts. The current synthetic strategy is a clean

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• chemistry and medicinal chemistry of naphthoquinones are the diversification of the strategies to obtain derivatives [8][80]. β-NQS are excellent electrophiles and have been used for obtaining naphthoquinones substituted by alkyl- or arylamines. The reactivity of aminopyrazolopyridine 30 with β-NQSNa (18

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• ligand and its appropriate steric properties are thought to be crucial to the success of the reaction [71]. The authors showed the in situ-formed 1,3-dienylmagnesium species 33 can also be trapped by a variety of electrophiles, demonstrating the synthetic utility of the reaction. In 2016, Fürstner and

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• intermediate 17a with R1 = Bn instead of R1 = bromobenzyl. Depending on the nature of the side chain R1 in compounds 12a–g, the reduction to compounds 17a–g leads to a change of R1 to a different side chain R1' which can be used for further transformation to R1'' by conversion with electrophiles. This was

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• synthesis of a wide array of heterocyclic compounds by creating C–C, C–N, C–O and C–S bonds due to their ability to act as electrophiles. The cyano group is considered as a versatile functional group in various organic syntheses because of its participation in various electrophilic, necleophilic and bipolar

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• nucleophilic addition reactions using isatin-derived imines 50 as electrophiles was reported by Tan, Shi and co-workers in 2020. Enantioenriched 3,3'-bisindoles with a biologically essential chiral 3-aminooxindole unit can be readily prepared by these methods. CPA 9 utilizes hydrogen bonding to activate both

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• give imines, iminium salts, aldehydes and other, in some cases dimeric products [49]. Here, oxidation of the benzylic amino moiety should lead either to iminium ions (or N-acyl iminium ions) 4a as strong electrophiles or to stabilized radicals 4b which could undergo cyclization to give the fluorenone

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• of prolinol silyl ether (cat. 120) and benzoic acid (A1) catalysts to bring about reaction between 3-formyl-substituted indoles or pyrroles 118 and diverse electrophiles, including carbonyls, imines and other Michael acceptors (Scheme 5) [69]. The reaction with secondary amines occurred via the